Short-course Fluoroquinolones in Acute Exacerbations of Chronic Bronchitis

Mark H Gotfried; Ronald F Grossman

Expert Rev Resp Med. 2010;4(5):661-672.

Abstract and Introduction

Abstract

It is estimated that 50–70% of acute exacerbations of chronic bronchitis (AECB) are caused by bacterial infections. Appropriate selection of antimicrobials may lead to better outcomes and reduced healthcare costs. Respiratory fluoroquinolones (moxifloxacin, levofloxacin and gemifloxacin) have a broad spectrum of activity against most AECB-causing pathogens and are used as first-line treatment in patients with comorbidity, severe airway obstruction or recurrent exacerbations. We review studies, identified through a MEDLINE search, that compared clinical efficacy and speed of recovery for short-course (≤5 days) fluoroquinolone therapy with commonly prescribed standard therapy (≥7 days). Among 177 studies reporting the use of fluoroquinolones for AECB treatment, 23 used a short-course regimen, shown to be at least as effective as standard therapy of 7 or more days duration. Furthermore, evidence suggests that short-course therapy offers faster resolution of symptoms, faster rate of recovery, fewer relapses, fewer and shorter hospitalizations, and longer time between recurrences.

Introduction

An acute exacerbation of chronic bronchitis (AECB) is characterized by increased sputum volume, increased sputum purulence, worsening dyspnea, cough and increased sputum tenacity.^[1,101] The first three of these symptoms, the cardinal symptoms, can be used to classify the exacerbation.^[101] AECB can have a substantial economic impact on patients, the healthcare system and society.^[2,3] Approximately 13 million individuals in the USA (4–6% of the adult population) have chronic bronchitis^[2,4] and experience an average of two to three acute exacerbation episodes per year.^[5] In the USA, more than 90% of patients with chronic bronchitis have sought treatment for their acute episodes, resulting in total healthcare costs of approximately US$1.6 billion.^[6]

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Next Section

Abstract and Introduction
Etiology
Antimicrobial Therapy for AECB
Short-course Fluoroquinolone Therapy
Methods
Results
Comparative Studies on Speed of Recovery
Discussion
Conclusion
Expert Commentary
Five-year View
References
Sidebar

Table 1. Comparative studies of short-course fluoroquinolone treatment with standard therapy in patients with acute exacerbations of chronic bronchitis.
Study (year)	Design	Patients (n)	Regimen	Duration (days)	Clinical outcomes (%)	Microbiology outcomes (%)	Ref.
*Levofloxacin*
Masterton and Burley (2001)	R, db, mc, mn	530	L: 500 mg q.d.	5	L: 82.8 (197/238)^†	L: 82.1 (92/112)^†	[37]
Masterton and Burley (2001)	R, db, mc, mn	530	L: 500 mg q.d.	7	L: 84.8 (207/244) 95% CI: -9.1–4.9 (day 14)	L: 83.2 (84/101) (day 14)	[37]
Martinez et al. (2005)	R, b, mc	394 uncomplicated	L: 750 mg q.d.	3	L: 93.0	L: 93.8 (75/80)	[38]
		394 uncomplicated	Az: 500 mg q.d. 250 mg q.d.	5	Az: 90.1% 95% CI: -9.6–3.8	Az: 90.1% 95% CI: -9.6–3.8
		369 complicated	L: 750 mg q.d.	5	L: 79.2	L: 81.4 (70/86)
		369 complicated	AC: 875 mg/125 mg b.i.d.	10	AC: 81.7 95% CI: -7.8–12.9	AC: 79.8 (71/89) 95% CI: -13.9–10.7
Grossman et al. (2006)	R, mc	369	L: 750 mg q.d.	5		L: 97.1 (297/306)	[26]
Grossman et al. (2006)	R, mc	369	AC: 875/125 mg b.i.d.	10		AC: 90.6 (242/267) (p < 0.001)	[26]
*Moxifloxacin*
Chodosh et al. (2000)	R, db	936	M: 400 mg q.d. M: 400 mg q.d. CL: 500 mg b.i.d.	5 10 10	M: 94 (127/135) M: 94 (136/144) CL: 95 (121/127) (days 10–16)	M: 94 (127/135) M: 95 (138/145) CL: 91 (115/127) (days 10–16)	[39]
					M: 94 (127/135) M: 96 (134/140) CL: 96 (118/123) (days 17–27)	M: 89 (127/143) M: 91 (135/148) CL: 85 (110/129) (days 17–27)
					M: 95 (274/288)^‡ M: 95 (266/281) CL: 94 (268/286) (days 10–16)	M: 93 (142/152)^‡ M: 95 (156/165) CL: 90 (130/144) (days 10–16)
					M: 94 (242/256) M: 97 (250/258) CL: 95% (232/245) (days 17–27)	M: 87 (130/149) M: 91 (144/159) CL: 83 (113/136) (days 17–27)
Urueta-Robledo et al. (2006)	R, db, mc, mn	563	M: 400 mg q.d.	5	M: 91 (201/221)	M: 92.8(128/138)	[40]
Urueta-Robledo et al. (2006)	R, db, mc, mn	563	L: 500 mg q.d.	7	L: 94 (203/216)	L: 93.8 (121/129)	[40]
Schaberg et al. (2001)	R, nb, mc, mn	575	M: 400 mg q.d. AC: 625 mg t.i.d.	5 7	M: 96.2 (251/261) AC: 91.6 (230/251) 95% CI: 0.4–8.7% (day 14)	M: 87.7 (64/73) AC: 89.6 (60/67) (day 14)	[27]
					M: 89.4 (227/254) AC: 87.5 (217/248) 95% CI: -3.5–7.5 (days 28–35)	M: 78.2 (68/87) AC: 80.5 (62/77) (days 28–35)
					M: 92.5 (270/292)^‡ AC: 85.2 (241/283) 95% CI: 2.2–12.54 (day 14)	M: 87.7 (64/73)^‡ AC: 89.6 (60/67) (day 14)
					M: 88.4 (244/276) AC: 85.0 (226/266) 95% CI: -2.1–9.2 (days 28–35)	M: 78.2 (68/87) AC: 80.5 (62/77) (days 28–35)
Starakis et al. (2004)	R, nb	153	M: 400 mg q.d. AC: 625 mg t.i.d.	5 7	M: 88.6 (70/79) AC: 89.2 (66/74) (day 14)	M: 90.9 (20/22) AC: 90.0 (18/20) (day 14)	[28]
Starakis et al. (2004)	R, nb	153	M: 400 mg q.d. AC: 625 mg t.i.d.	5 7	M: 90.0 (63/70) AC: 89.4 (59/66) (days 28–35)	M: 90.0 (18/20) AC: 88.9 (16/18) (days 28–35)	[28]
DeAbate et al. (2000)	R, db, mc	567	M: 400 mg q.d. Az: 500 mg q.d. 250 mg q.d.	5 1 4	M: 88 (194/221) Az: 88 (214/243)	M: 95 Az: 94	[29]
Grassi et al. (2002)	R, mc	476	M: 400 mg q.d. Cx: 1 g q.d.	5 7	M: 90.6 (193/213)^† Cx: 89.0 (187/210) 95% CI: 0.634–2.258	M: 91.7 (33/36) Cx: 93.3 (28/30)	[30]
Wilson et al. (1999)	R, db, mc, mn	750	M: 400 mg q.d. CL: 500 mg b.i.d.	5 7	M: 89 (287/322)^‡§ CL: 88 (289/327) 95% CI: -3.9–5.8 (day 14)	M: 77 (89/115) CL: 62 (71/114) 95% CI: 3.6–26.9 (day 14)	[31]
Wilson et al. (1999)	R, db, mc, mn	750	M: 400 mg q.d. CL: 500 mg b.i.d.	5 7	M: 89 (256/287) CL: 89 (257/289) (days 21–28)	M: 80 (71/89) CL: 78 (55/71) (days 21–28)	[31]
Wilson et al. (2004)	R, db, mc, mn	730	M: 400 mg q.d. A: 500 mg t.i.d. CL: 500 mg b.i.d. Cf: 250 mg b.i.d.	5 7 7 7	M: 87.2 (239/274)^† A: 81.5 CL: 87.4 Cf: 83.8	M: 91.5 (65/71)^† A + CL + Cf: 81% (64/79)	[32]
					Combined all three comparators 95% CI: -3.0–8.5	Combined all three comparators 95% CI: 0.4–22.1
					M: 87.6 (310/354)^‡ A: 83.0 CL: 84.2 Cf: 82.2	M: 76.8 (86/112)^‡ A + CL + Cf: 67.5 (81/120)
					Combined all three comparators 95% CI: -0.7–9.5	Combined all three comparators 95% CI: -1.8–20.4
Wilson et al. (2006)	R, db, mc, mn	730	M: 400 mg q.d. A: 500 mg t.i.d. CL: 500 mg b.i.d. Cf: 250 mg b.i.d.	5 7 7 7	71 (251/354)^§ 63 (487/730) (p = 0.020)		[41]
Zervos et al. (2007)	R, mc	342	M: 400 mg q.d. Az: 500 mg q.d.	5 3	M: 90 (149/165)^† Az: 90 (147/164) (days 10–12)	M: 84 Az: 93 (days 10–12)	[33]
Zervos et al. (2007)	R, mc	342	M: 400 mg q.d. Az: 500 mg q.d.	5 3	M: 82 (132/162)^† Az: 81 (133/164) (days 22–26)	M: 73 (40/55) Az: 89 (42/46) (days 22–26)	[33]
*Gemifloxacin*
Sethi et al. (2004)	R, db	360	Ge: 320 mg q.d. L: 500 mg q.d.	5 7	Ge: 97.5 (156/160)^† L: 93.5 (145/155) 95% CI: -0.61–8.51 (days 5–7)	Ge: 87.5^† L: 90.4 (days 5–7)	[42]
					Ge: 88.2 (134/152) L: 85.1 (126/148) 95% CI: -4.67–10.72 (days 14–21)	Ge: 78.4 L: 85.7 (days 14–21)
					Ge: 83.7 (123/147) L: 78.4 (109/139) 95% CI: -3.83–14.34 (days 28–35)	Ge: 77.8 L: 70.5 (days 28–35)
					Ge: 94.0 (171/182)^‡ L: 88.8 (158/178) 95% CI: -0.60–10.98 (days 5–7)	Ge: 81.8^‡ L: 86.7 (days 5–7)
					Ge: 85.2 (155/182) L: 78.1 (139/148) 95% CI: -0.9–15.05 (days 14–21)	Ge: 75.0 L: 80.0 (days 14–21)
					Ge: 80.8 (123/147) L: 70.8 (109/139) 95% CI: 1.18–18.78 (days 28–35)	Ge: 75.0 L: 65.0 (days 28–35)
Wilson et al. (2002)	R, db, mc, mn	712	Ge: 320 mg q.d. CL: 500 mg b.i.d.	5 7	Ge: 85.4 (300/351)^† CL: 84.6 (303/358) 95% CI: -5.0–6.6	Ge: 86.7 (39/45)^† CL: 73.1 (38/52) 95% CI: -2.0–29.2	[7, 43]
El Moussaoui et al. (2008)	R, db, mc, mn	712	Ge: 320 mg q.d. CL: 500 mg b.i.d.	5 7	PP population Ge: 79.5 (279/351)^‡ CL: 78.2 (280/358) ITT population (days 13–24)	Ge: 75.4 (43/57)^‡ CL: 63.6 (42/66) 95% CI: -4.3–27.9 (days 13–24)	[7, 43]
Wilson et al. (2003)	R, db, mc, mn	272	Ge: 320 mg q.d. Cx: 1 g iv. q.d. Cf: 500 mg b.i.d.	5 3 7	Ge: 86.8 (105/121)^† Cx/Cf: 81.3 (91/112) 95% CI: -3.9–14.9	Ge: 62.5 (30/48)^† Cx + Cf: 60.8 (31/51) 95% CI: -17.4–20.9	[34]
Wilson et al. (2003)	R, db, mc, mn	272	Ge: 320 mg q.d. Cx: 1 g iv. q.d. Cf: 500 mg b.i.d.	5 3 7	PP population 82.6 (114/138)^† 72.1 (98/136) 95% CI: 0.7–20.4 ITT population (2–4 days post-therapy)	Ge: 62.5 (30/48)^† Cx + Cf: 60.8 (31/51) 95% CI: -17.4–20.9	[34]
File et al. (2000)	R, db, mc	600	Ge: 320 mg q.d. AC: 500/125 mg t.i.d.	5 7	Ge: 93.6 AC: 93.2 95% CI: -3.9–4.6	Ge: 90.9 AC: 79.5 95% CI: -3.3–26.0	[35]
Ball et al. (2001)	R, db, mn	617	Ge: 320 mg q.d. T: 200 mg q.d.	5 5	Ge: 91.5^† T: 87.6	Ge: 86.8^† T: 82.4	[44]

^†Per-protocol population.
^‡Intent-to-treat population.
^§Studies in which clinical cure rate was measured; clinical success rate was analyzed in the majority of the studies.
A: Amoxicillin; AC: Amoxicillin and clavulanate; Az: Azithromycin; b: Blinded; b.i.d.: Twice-daily; Cf: Cefuroxime axetil; CL: Clarithromycin; Cx: Ceftriaxone; db: Double-blind; Ge: Gemifloxacin; ITT: Intent-to-treat; iv.: Intravenous; L: Levofloxacin; M: Moxifloxacin; mc: Multicenter; mn: Multinational; nb: Nonblinded; PP: Per protocol; q.d.: Once daily; R: Randomized; T: Trovafloxacin; t.i.d.: Three-times daily.

Table 2. Antibiotic therapy and speed of recovery from acute exacerbations of chronic bronchitis.
Antibiotic treatment	Regimen	Duration (days)	Fast recovery (%) (<5 days) (n = 659)	Slow recovery (%) (>5 days) (n = 505)
Moxifloxacin	400 mg q.d.	5	70.3	29.7
Clarithromycin	500 mg b.i.d.	10	49.7	50.3
Co-amoxiclav	500/125 mg t.i.d.	10	44.4	55.6

The moxifloxacin treatment regimen was statistically significantly better than the other two treatment regimens (p < 0.0001).
b.i.d.: Twice-daily; Co-amoxiclav: Amoxicillin/clavulanate; q.d.: Once daily; t.i.d.: Three-times daily.
Adapted from [46].

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